Mass spectrometry is a technique whose value for analyses in pharmacology and toxicology is well established. The long-term objective of the program described here is the extension of the powerful analytical capabilities of mass spectrometry to a series of problems in pharmacology and toxicology which, for various reasons, have not been previously susceptible. The program includes the development of flexible new instrumental techniques, and the development of efficient isolation, purification and derivatization procedures which are prerequisite to successful mass spectral analysis of drug metabolites and natural products. Our research in pharmacology will be primarily directed to two areas. In one we seek to elucidate the structures and kinetics of circulation of the activated human metabolites of the anti-neoplastic drug cyclophosphamide, and to study the mode of action of this drug. Research in the second area will be development of simple, sensitive, general procedures for analyses of intact glucuronide conjugates of drug metabolites and natural products. These procedures will be used to elucidate the chemical structure of conjugated metabolites of cholecalciferol and dihydrotachysterol, and to evaluate their excretion as it is associated with various kinds of Vitamin D resistance. Our research in toxicology will center on the elucidation of the chemical structures of excretable, and thus detoxified, derivatives of bilirubin formed in photography. The principles and analytical potential of charge exchange ionization will be explored, as an alternative to electron impact and chemical ionization, which is still compatible with the introduction of samples into the mass spectrometer through a gas chromatograph.